Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic State

Published on 07/03/2015 by admin

Filed under Critical Care Medicine

Last modified 22/04/2025

Print this page

rate 1 star rate 2 star rate 3 star rate 4 star rate 5 star
Your rating: none, Average: 0 (0 votes)

This article have been viewed 1442 times

Chapter 50 Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic State

Joel J. Schnure, MD , Jack L. Leahy, MD

1 What is diabetic ketoacidosis (DKA)?

DKA is a serious acute metabolic decompensation in persons with known or newly presenting diabetes. It is a consequence of a relative or an absolute insulin deficiency in combination with an excess of counterregulatory hormones (primarily glucagon and catecholamines, but also cortisol and growth hormone). The classic triad of features is hyperglycemia (typically > 250 mg/dL), anion gap metabolic acidosis, and ketosis.

2 Describe the tissue actions of insulin

The major action of endogenously secreted or injected insulin is to lower blood glucose level by increasing glucose uptake into peripheral tissues such as skeletal muscle and adipose and by promoting glycogen production and stopping gluconeogenesis in the liver. Additionally its anabolic effects inhibit adipose breakdown to free fatty acids and muscle breakdown to amino acids. The sensitivity of these actions differs in the various target tissues, with small amounts of insulin fully preventing triglyceride metabolism and release of free fatty acids from adipose tissue whereas larger amounts are needed for suppression of hepatic glucose production and to promote glucose clearance into peripheral tissues.

3 What is the pathogenesis of DKA?

DKA starts withabsolute insulin deficiencybecause of a broken or clogged insulin pump, missed injections, or progression of an unknown illness to overt insulin deficiency or withrelative insulin deficiencyfrom a rise in tissue insulin requirements from infection, trauma, or other stresses. Glucose production from the liver increases, and glucose clearance into peripheral tissues is impaired, causing the blood glucose level to rise. Stress-related increases in counterregulatory hormones exacerbate these effects. As the renal glucose threshold is passed, an osmotic diuresis occurs causing urinary losses of water and electrolytes. The ensuing dehydration further increases the level of catecholamines. Also, because glucagon and insulin levels are normally inversely related, the insulin deficiency causes hyperglucagonemia. The increased catecholamines and glucagon and the insulin deficiency promote excess release of fatty acids from the adipose tissue that further impairs insulin-mediated glucose uptake into peripheral tissues. The capacity of the liver for β-oxidation of the fatty acids is exceeded, resulting in ketone production. This ketonemia and the resulting acidosis often cause nausea and vomiting; the patient’s polydipsia therefore stops, worsening the dehydration. The patient is now in DKA with this whole process occurring over a 12- to 48-hour period. This sequence of events is depicted inFigure 50-1.

image

Figure 50-1 Pathogenesis of DKA.

(From Atlee J: Complications in Anesthesia, 2nd ed. Philadelphia, Saunders, 2007.)

4 How does DKA cause an anion gap metabolic acidosis?

The insulin deficiency and increased glucagon and catecholamines cause excess release of fatty acids from the adipose tissue and activation of metabolic pathways in the liver for conversion to ketoacids: acetoacetate, acetone, and β-hydroxybutyrate. Their accumulation results in the anion gap metabolic acidosis that is characteristic of DKA. Theanion gapis calculated by subtracting the serum concentration of the major anions (chloride and bicarbonate)from the main cation (sodium). A difference of greater than 12 mEq/L along with a lowered bicarbonate level (<15 mEq/L) shows the presence of anions that are not identified in this calculation, thus the anion gap (in this case the ketoacids).

5 How is type 1 diabetes diagnosed?

Type 1 diabetes results from autoimmune-mediated destruction of islet beta cells. Most patients therefore present with signs and symptoms of insulin deficiency: exhaustion, weight loss, nocturia, thepolys(polyuria and polydipsia), and sometimes DKA. It is usually diagnosed because of a typical clinical presentation and can be confirmed with use of specific markers for the autoimmune beta cell destruction. The best known is glutamic acid decarboxylase-65 (GAD-65) antibody, which is directed against a beta cell enzyme called glutamic acid decarboxylase. A positive test confirms type 1 diabetes, but a negative test does not rule it out. It is not necessary to perform GAD-65 antibody testing in all patients with newly identified type 1 diabetes, but it is most useful in those with elements of both type 1 and type 2 diabetes. In contrast, insulin or C peptide testing is not recommended, because insulin secretion is driven by glycemia, and the patient’s hyperglycemia and short duration of diabetes mean that these measures are rarely absent in patients with new-onset type 1 diabetes.

6 Does DKA develop in persons with type 2 diabetes?

Most series of persons with DKA show a 10% to 30% incidence of type 2 diabetes usually in association with an accompanying severe medical illness. The concept is that the added stress of the associated illness allows ketoacidosis to occur, in part because catecholamines are potent inhibitors of insulin secretion from the beta cell. This accompanying illness also impacts the course. Mortality rates are much higher in persons with DKA who are older than 50 years of age versus younger patients, with the older group dying of sepsis, adult respiratory distress syndrome, shock, or cardiovascular collapse.

A form of type 2 diabetes also exists that is ketosis prone, so-calledFlatbush diabetesorketosis-prone type 2 diabetes. These patients are mostly from minority populations (most studied are black and Latino) who have ketosis and sometimes DKA, often with obesity, but test negative for markers of type 1 diabetes. The defining clinical feature is being able to stop insulin months later, sometimes permanently. The pathogenesis is thought to be a heightened sensitivity for suppression of insulin secretion during stress that partially reverses with time.

7 What are the common precipitating events for DKA?

The most frequent initiating events for DKA are infection, insulin underdelivery, and newly presenting type 1 diabetes. Cardiovascular events and cerebrovascular accidents also occur, mostly in older patients. Insulin omission used to be most common in teenagers and young adults, although the growing use of insulin pumps in all ages means DKA from pump failure or catheter occlusion is age independent. Among infections pneumonias, gastrointestinal tract viral infections, and urinary tract infections are most common. Other causes are pancreatitis, drug abuse, or severe medical illness of any type. Even with all of the known causes, failure to identify a precipitating event is relatively common.

8 Describe the common signs and symptoms of DKA

Patients typically describe 1 to 3 days of polyuria, nocturia, and thirst. Fatigue also occurs, and often a rapid weight loss reflects the catabolic effect of the insulin deficiency and volume depletion. As the ketonemia and metabolic acidosis progress, nausea and repeated vomiting may occur, exacerbating the dehydration. Abdominal pain is also common related to gastric distention from the metabolic acidosis or irritation from repeated vomiting. Patients may report shortness of breath from their Kussmaul respirations that can be mistaken for a pulmonary infection or cardiac event. What is not usually reported is confusion or coma; fewer than 20% of patients are stuporous or show any confusion.

On examination, patients often show the Kussmaul breathing pattern of deep, sighing breaths as they attempt to compensate for the metabolic acidosis by lowering their PCO2. Tachycardia is common. In contrast the systolic blood pressure is rarely less than 100 mm Hg because of the osmotic effect of the hyperglycemia keeping fluid in the vascular space. Body temperature is usually normal even when an infection is present because the metabolic acidosis blunts the fever response. A distinguishing feature of DKA is the fruity sweet smell of the patient’s breath from their exhaling the ketone acetone. The remainder of the physical examination is typically unremarkable except for a generalized abdominal tenderness.

9 How does the hyperosmolar hyperglycemic state (HHS) differ from DKA?

HHS also is characterized by profound hyperglycemia but without ketoacidosis. The distinguishing clinical features of HHS are as follows:

image Occurs most often in the elderly and those with known type 2 diabetes

image Very high blood glucose levels of 600 mg/dL or greater

image Markedly elevated serum osmolarity of 320 mOsm/kg or greater

image Frequent occurrence of altered mental state or coma

image More serious hypotension and overt dehydration including substantially larger electrolyte losses than DKA

image High mortality rate that averages 15% versus less than 2% in uncomplicated DKA

10 What is the pathogenesis of HHS?

The major difference from DKA is a modestly higher circulating insulin level that prevents much of a rise in free fatty acids and thus blocks ketone production from the liver but is not enough to suppress hepatic glucose production or promote glucose clearance into peripheral tissues. Therefore the main feature is hyperglycemia without ketoacidosis, although small amounts of urinary ketones and a modest widening of the anion gap can be seen. As such the metabolic acidosis–induced vomiting and abdominal pain that are common in DKA, and often are what gets the patient to seek medical help, are lacking. Instead the worsening hyperglycemia and osmotic diuresis go on for much longer, typically many days or a couple of weeks, and the presentation is often insidious, manifesting in symptoms such as bed-wetting or modest confusion that may be unnoticed in the elderly. Thus the dehydration and urinary electrolyte losses are considerably worse than in DKA, and it is this dehydration that is the key feature leading to HHS by causing a fall in urine output and with it glycosuria. The blood glucose level now rises above the renal threshold to values that can exceed 1000 mg/dL. Serum osmolarityrises in parallel, and the resulting confusion or coma is usually why the patient is brought for medical attention.

11 What are the common precipitating events in HHS?

HHS occurs most often in patients with known type 2 diabetes although it is the first evidence of diabetes in 30% to 40% of patients. The most common cause is a medical crisis such as infection or sepsis, cardiovascular event, cerebrovascular accident, pancreatitis, or acute abdomen. Pharmaceuticals that raise glycemia also are sometimes at fault, with the best known high-dose thiazides, corticosteroids, sympathomimetic agents, atypical antipsychotics, and β-blockers. Another common feature is caregivers having restricted the patient’s access to water because of incontinence or bed-wetting.

12 Describe the common signs and symptoms of HHS

Patients are usually brought for medical evaluation because of a mood change, fall-off in appetite, confusion, or coma. Particularly common are subtle behavior changes over several weeks such as lethargy or less interaction with the family. Also hints to the precipitating cause or illness may be elicited. Useful history is a worsening of bed-wetting or incontinence to gauge the duration of the osmotic diuresis.

On examination, patients typically show some mental alteration from slow answers to questions or searching for words to obtundation or coma. Because of the advanced age of many of these patients and the potential for underlying central nervous system (CNS) pathologic conditions, they may have focal findings that mimic a stroke. In addition, these patients usually are seen with signs of severe volume depletion such as marked hypotension, dry mucous membranes, and skin tenting. As with DKA, the absence of a fever does not exclude infection especially because of the blunted fever response in elderly patients.

13 Which initial laboratory tests are obtained in DKA and HHS?

Laboratory testing at presentation includes a complete blood cell count, serum electrolytes, arterial blood gases, serum creatinine, serum ketones including β-hydroxybutyrate when available, a Chem 12 panel, and urinalysis for signs of infection. In DKA, radiographs or scans, pan-cultures, drug screens, and serum brain natriuretic peptide, lactate, lipase, or markers of ischemic cardiac damage are not usually obtained without suggestive history or physical findings. In HHS because of the advanced age of many patients and the insidious nature of the presentation, pan-testing is common particularly in patients who are confused or comatose: urine and blood cultures, electrocardiogram, cardiac enzymes, and CNS imaging, especially if there are focal neurologic findings. Hemoglobin A1ctesting is very helpful to determine the patient’s diabetes control before the acute hyperglycemic event or the chronicity of hyperglycemia in patients with new-onset diabetes.

14 How and when to test for ketones?

Testing for ketones in the serum or urine is done with the nitroprusside reaction that gives a semiquantitative estimate of acetoacetate and acetone levels. However, it does not recognize β-hydroxybutyrate. Therefore the severity of DKA may be underestimated if the ratio of β-hydroxybutyrate to the others is increased as can occur with lactic acidosis or alcohol. The common observation of the ketone reaction becoming more positive during therapy when the patient is clinically improving represents conversion of β-hydroxybutyrate to acetoacetate during metabolic breakdown of that ketone body. As such, it is recommended to test serum ketones only at presentation. Direct measures of serum β-hydroxybutyrate are increasingly available and have been advocated as a better diagnostic test for DKA than urine ketones but also not for repeated monitoring. However, the Joint British Diabetes Societies have recently recommended bedside monitoring of blood ketones during therapy because of the availability of reliable handheld meters.

15 How to interpret the complete blood cell count results in DKA and HHS?

The white blood cell (WBC) count is usually elevated in DKA, sometimes to 20,000 or 25,000/mm3, with a leftward shift from stress hormone–induced demargination. The WBC count typically returns to the normal range in several hours to a day of treatment of the DKA. In contrast, hemoglobin and hematocrit values are typically normal unless a prior abnormality such as chronic renal impairment exists. Therefore a large decrease from the patient’s pre-DKA baseline hemoglobin level should be evaluated for gastrointestinal bleeding or another source of internal or external hemorrhage.

The findings in HHS are more varied because of the older age of many of the patients and the presence of preexisting comorbidities or severe precipitating illnesses. A stress-induced leukocytosis is common but unlike in DKA may persist for a few days from the prolonged course of treatment in many patients. Dehydration is also more severe than in DKA, and a fall in hemoglobin level by 1 to 3 g with rehydration is often seen.

16 What changes in serum sodium level occur in DKA and HHS?

The osmotic diuresis in DKA and HHS results in large total-body reductions in volume and electrolytes. Impaired water intake is also a common feature both from the nausea and/or vomiting in DKA and the blunted thirst response of the elderly in HHS. Still, serum sodium is usually below normal in DKA because of the osmotic effect of the hyperglycemia drawing cellular and interstitial fluid into the vascular space. The sodium concentration of this fluid is less than in blood (intracellular fluid is only 3-5 mEq), diluting the serum sodium concentration, an effect termedpseudohyponatremia. One can correct for this effect by adding 1.6 mEq/L of sodium to the measured value for every 100 mg/dL of glucose above the normal 100 mg/dL.

The sodium concentration in HHS is a major contributor to the hyperosmolarity as it is often normal or above the normal range despite the marked hyperglycemia. This is because of the protracted diuresis of hypotonic urine that is a key pathogenic factor in HHS resulting in a greater whole-body water deficit versus DKA. An additional feature in many patients is continued use of diuretics that exacerbate the urinary water losses.

17 What are the changes in serum potassium level in DKA and HHS?

In DKA, serum potassium level is altered by an adaptation to the metabolic acidosis of an electroneutral shift of H+out of blood into cells in exchange for K+from cells back to blood. A formula to estimate the serum potassium at physiologic pH is 0.8 mEq of potassium for every 0.1 pH from 7.4. This shift explains the high level of concern overnormalpotassium levels in patients with acidosis and how treatment with bicarbonate could cause a hypokalemic crisis. In addition, serum potassium losses persist during early DKA therapy related to the effect of insulin to drive potassium into cells and additional urinary losses from the osmotic diuresis until the hyperglycemia is controlled. Thus DKA is characterized by large reductions in total-body potassium that are not accurately reflected in the initial serum potassium level.

In HHS, the lack of significant acidosis means there is little K+-H+exchange effect. Still, whole-body potassium losses typically exceed those seen with DKA, and there are the ongoing losses during treatment; therefore the concern over low or low-normal potassium levels is equal to that of DKA.

18 How is the anion gap calculated and interpreted?

The anion gap is calculated by subtracting the serum concentrations of chloride and bicarbonate from the sodium concentration. A difference of greater than 12 mEq/L along with a lowered bicarbonate level (<15 mEq/L) shows the presence of an anion gap metabolic acidosis and is a defining feature of DKA. Other causes of anion gap metabolic acidosis are lactic acidosis, advanced renal failure, and ingestion of high-dose salicylates, methanol, or ethylene glycol. Some patients with DKA have a complex acid–base disorder that can include a metabolicalkalosis from protracted vomiting or the marked dehydration, and/or a respiratory alkalosis from fever, pain, or an accompanying pulmonary or CNS illness.

In HHS, the anion gap is often modestly increased from increased lactate because of the marked dehydration, but the bicarbonate level is greater than 15 mEq/L and pH is greater than 7.3.

19 How is hyperosmolarity calculated in HHS?

The defining clinical feature of HHS is hyperosmolarity. The normal serum osmolarity is 275 to 295 mOsm/L. It is made up of the osmotic effects of serum sodium, potassium, glucose, and urea. However, urea traverses membranes relatively freely and thus does not contribute to the serum tonicity that is also called theeffective osmolarity,which is calculated by using the following formula:

image

A relatively linear relationship exists between the effective osmolarity and mental state in HHS, with deficits beginning to occur at values above 320 mOsm/L and coma above 340 mOsm/L. As such, stupor or coma in a patient with hyperglycemia with values below 320 mOsm/L warrants a careful work-up for other causes of the mental status change.

Mortality also rises substantially with levels above 350 mOsm/L.

20 What are the goals of therapy in DKA?

The main pathogenic features of DKA are dehydration, insulin deficiency, and an excess of stress hormones that collectively cause the hyperglycemia and metabolic acidosis. Treatment goals are as follows:

image Reverse the ketogenesis and return the pH to normal.

image Restore blood glucose control.

image Correct the hypovolemia.

image Replete the whole-body electrolyte stores.

image Identify and reverse any precipitating illness.

image Prevent the complications that can occur during DKA therapy.

21 Describe insulin therapy for DKA

DKA is usually treated with a continuous intravenous (IV) infusion of regular insulin at 0.1 unit/kg per hour. Hourly intramuscular injections or 2-hour subcutaneous injections of a rapid-acting insulin at the same amounts as the IV insulin can be used when IV insulin is not possible. Once insulin is started, blood glucose level should fall 50 to 70 mg/dL per hour. If it does not, the recommendation after 2 hours is to double the insulin dose hourly until that occurs. The insulin infusion is continued until the blood glucose level falls below 200 mg/dL and then is lowered by 50% along with switching the IV fluids to contain 5% dextrose (D5) or 10% dextrose to keep the blood glucose level between 100 and 200 mg/dL. The insulin infusion is also continued for another 6 to 12 hours to prevent recurrence of the ketoacidosis. A controversial issue is whether to give a bolus of insulin before starting the infusion because studies have failed to show a benefit of the bolus approach. Still it is commonly used because many believe it gets therapy started while the patient is being fully evaluated, and they give 10 units of regular insulin rapidly IV, believing that gives an hour before the infusion must be started.

22 What is appropriate fluid therapy in DKA?

The osmotic effect of the hyperglycemia keeps the vascular space relatively fluid replete as the DKA develops. Administering insulin without fluid can reverse this effect and cause cardiovascular collapse. Unless an illness prevents aggressive fluid replacement such as chronic renal failure with anuria or congestive heart failure, 1 L of normal saline solution is usually given quickly followed by isotonic saline solution or half-normal saline solution at 300 to 500 mLper hour depending on the patient’s sodium level. Potassium is added to the IV fluids as described below. Glucose is also added to the IV fluids once blood glucose is brought below 200 mg/dL to prevent hypoglycemia while the insulin infusion is continued for full reversal of the ketogenesis. The fluid deficit in DKA is up to 100 mL/kg, but larger volumes are often needed to restore euvolemia, because much of the infused volume over the first 5 to 6 hours is lost in the urine until glycemia is below the renal threshold. A common finding after closure of the anion gap is a subnormal serum bicarbonate and raised chloride level. This hyperchloremic metabolic acidosis occurs because of the large amount of NaCl in the administered IV fluids, plus the loss of ketones in the urine that equates to a loss of “bicarbonate equivalents,” because bicarbonate is regenerated as the ketones are metabolized during the DKA therapy. However, it is harmless and reverts to normal over a few days without therapy.

23 Describe potassium replacement in DKA

Whole body potassium stores are lowered 150 to 250 mEq in DKA. This depletion is usually not apparent in the initial serum potassium because of the H+-K+cellular shift, with the potential for severe hypokalemia and life-threatening arrhythmias with low or normal potassium levels at presentation without adequate replacement. Usually 20 to 40 mEq of KCl is included in all IV bags after the initial liter of run in saline solution, except if the potassium level exceeds 5.5 mEq/L. In that case, potassium is added to the IV fluids as soon as the potassium level falls below 5.5 mEq/L. In addition, oral potassium supplements can be given to patients with a high risk of treatment-associated hypokalemia in the absence of severe nausea or vomiting. After the first few liters of IV fluids, some clinicians replace the KCl with potassium phosphate in 1 or 2 L of IV fluid, because insulin drives phosphorus intracellularly so that a common finding in DKA 12 to 24 hours after starting therapy is hypophosphatemia. However, this is not supported by evidence-based outcomes, because trials of phosphate replacement in DKA have not shown a benefit. Many authors recommend phosphate replacement only for phosphate levels below 1 mmol/L.

24 How are patients’ conditions monitored during DKA therapy?

Bedside fingerstick glucose, inputs and outputs, and vital signs are monitored hourly. Every-2-hour measures are serum glucose and electrolytes to monitor the K+, Na+, and anion gap. Once the anion gap is closed and the blood glucose falls below 200 mg/dL, a bedside glucose level is monitored every 1 to 2 hours and electrolytes every 4 to 6 hours to confirm reversal of the ketoacidosis as indicated by continued normalization of the anion gap.

25 When is bicarbonate given?

Studies have failed to show any benefit of bicarbonate in patients with DKA. Concerns also exist that the rapid rise in pH could acutely lower the serum potassium. It is recommended that bicarbonate be given only with life-threatening acidosis, with most authors advocating a pH threshold of below 6.9. Then up to 100 mmol of sodium bicarbonate diluted in 400 mL sterile water plus 20 mEq KCl can be administered over a 2-hour period.

26 How is the patient transitioned from the insulin infusion?

Closure of the anion gap, along with clinical stability in terms of volume status and resolution of the marked hyperglycemia and symptoms such as nausea or vomiting, signifies cessation of the DKA. The insulin and fluid-electrolyte infusions are continued for another 12 hours if possible as recurrence of ketoacidosis from turning off the infusion too fast is a common occurrence. The patient’s usual therapy is then restarted—pump or injections—at the prior doses or adjusted as needed on the basis of the hemoglobin A1clevel at presentation and reported home blood glucose values. It is necessary to wait 2 to 3 hours after restarting the subcutaneous insulin before turning off the insulin infusion.

27 Is the treatment of DKA in children different than in adults?

The general recommendations for diagnosis, therapy, and monitoring in children with DKA are similar to those for an older population. One difference is that children are treated in acute-care settings whereas, increasingly, uncomplicated DKA in adults is treated in emergency departments or monitored noncritical beds. The fluid and electrolyte replacement is also appropriate to the size and age of the child. Insulin infusion rates in preschool children are often started at 0.05 units/kg per hour, but in older children it is 0.1 unit/kg per hour as in adults. One issue of great concern in children is cerebral edema during the DKA treatment. Although uncommon, DKA-related cerebral edema occurs almost exclusively in children and is often fatal. Studies have shown some degree of brain swelling in virtually all children during DKA therapy although the clinical syndrome of acute onset of altered mental state or frank coma is rare.

28 Is the treatment of DKA in pregnancy different?

Elements of the adaptive physiology of pregnancy have the potential to increase the risk of marked hyperglycemia and DKA in women with type 1 diabetes. Human placental lactogen, along with growth hormone and prolactin, markedly impairs insulin sensitivity. There is also an accelerated lipolytic rate during normal pregnancy. In addition, the expanding abdominal girth causes rapid shallow breathing and a respiratory alkalosis that leads to a compensatory wasting of bicarbonate in the urine, lowering the patient’s buffering capacity. Still, DKA is uncommon in pregnant patients, in part reflecting today’s intensive diabetes management in pregnancy. When seen, DKA in a pregnant patient may be the first sign of diabetes or occur because of a broken pump or from an infection. The treatment is similar to that in nonpregnant patients, with mortality rates that are similarly low. On the other hand, older statistics that are still quoted suggest a high fetal loss rate: one review reported 9%.

29 What are the goals of therapy in HHS?

The main feature of HHS is extreme dehydration that results in marked hyperglycemia and hyperosmolarity-induced mental status changes. These patients frequently present with a precipitating illness that may be the main medical focus. As such, the primary goal is restoration of the vascular volume and electrolytes. Although insulin is usually needed for full blood glucose control, volume replacement will improve most of the metabolic derangements including inducing a marked fall in glycemia. The other major goal is to identify and start therapy for the precipitating illness. Because of the advanced age and comorbidities of many of these patients, plus their altered mental state and frequency of a serious accompanying illness, these patients are almost always treated in an intensive care unit (ICU) setting. The goals are as follows:

image Correct the hypovolemia for hemodynamic stability, and restore renal perfusion and glycosuria.

image Identify and reverse any precipitating illness.

image Recover blood glucose control.

image Slowly reverse the hyperosmolarity with return to the patient’s baseline mental state.

image Replete whole-body electrolyte stores.

image Prevent the complications that can occur with HHS therapy.

30 What is appropriate fluid therapy in HHS?

Because the fluid and electrolyte losses in HHS are typically greater than in DKA, patients often have hypotension or are in shock. The first priority is to restore adequate intravascular volume and renal perfusion followed by a gradual return to euvolemia and normal electrolyte stores. A liter or more of 0.9% saline solution is given quickly, especially to patients who have hypotension or are in shock unless a complicating issue exists such as renal failure with anuria or congestive heart failure. Several methods are then used to determine whether to continue with 0.9% saline solution or reduce the osmotic load by switching to half-normal saline, with the more dilute fluid recommended when the corrected sodium is at or above the normal range, or for an effective osmolarity of greater than 330 mOsm/L. Because the rate of the fluidreplacement is individualized, the serum osmolarity is lowered no more than 3 mOsm hourly to minimize risk of cerebral edema. Another common guideline is to replace half of the patient’s fluid deficit in the first 12 hours and the remainder over the next 12 to 24 hours, again to prevent rapid changes in tonicity that could precipitate cerebral edema. This is particularly important in pediatric patients with HHS who are at highest risk for cerebral edema; it is recommended they receive no more than 50 mL/kg of saline solution over the first 4 hours, with correction of the remaining fluid deficit over 48 hours versus the 24 hours in adults. As in DKA, 20 to 40 mEq of potassium is added to each liter of IV fluids after the initial run in saline solution. Glucose-containing IV fluids are started earlier than in DKA, once the blood glucose falls below 250 to 300 mg/dL, along with titration of the insulin infusion to keep the blood glucose level between 100 and 200 mg/dL.

31 How is a patient’s water deficit calculated?

The average fluid deficit in HHS is 100 to 200 mL/kg or 8 to 12 L. A patient’s total body water deficit can be calculated with use of the following assumptions and formula. Body water is 60% of the body weight in men and 50% in women. The patient’s corrected sodium is calculated by adding 1.6 mEq/L of sodium to the measured value for every 100 mg/dL of glucose above 100 mg/dL. This value minus a normal sodium concentration of 140 mEq/L divided by 140 gives the percent deviation from the normal sodium concentration. Multiplying it by the patient’s calculated total body water gives the fluid deficit. For instance, a 100 kg man with a glucose level of 800 mg/dL and measured sodium concentration of 145 mEq/L:

image

image

image

32 Describe insulin therapy for HHS

Unlike in DKA where immediate insulin replacement is required to reverse the ketoacidosis, in HHS insulin therapy is secondary to restoration of the intravascular volume. Only after fluid support has been established and the patient is hemodynamically stable is insulin begun. It is administered as an IV infusion at 0.1 unit/kg, with or without an initial bolus as preferred by the caregivers. The goal is to lower the glucose level by 50 to 70 mg/dL per hour after the large drop from the initial fluid push. Thus the insulin infusion rate is adjusted hourly up or down until the blood glucose falls below 250 to 300 mg/dL, and then it is lowered by 50% along with switching the IV fluids to contain D5, with continued hourly titration to keep the blood glucose level between 100 and 200 mg/dL. The clinical course of these patients often entails a lengthy ICU admission related to comorbidities, with maintenance of the insulin infusion until the patient is medically stable. The patient’s usual therapy is then restarted or changed as deemed appropriate. Unlike in DKA, some patients do not require long-term insulin therapy after HHS.

33 What complications can occur in DKA and HHS?

Today’s aggressive fluid and potassium replacement along with close monitoring of patients during treatment of DKA and HHS has markedly reduced the risks of hypotension and shock related to correction of hyperglycemia without adequate volume replacement, hypoglycemia, and severe hypokalemia. A key principle in comatose patients is protection of the airway and prevention of aspiration. Severe and at times life-threatening complications still can occur, sometimes in patients who have responded well to therapy but whose conditions then rapidly deteriorate, often with no identifiable cause: disseminated intravascular coagulation, acute respiratory distress syndrome, rhabdomyolysis, cerebral edema, and various thromboembolic events such as pulmonary embolus, stroke, bowel infarction, or myocardial infarction. Some authors recommend prophylaxis against thromboembolic events especially in severely dehydrated patients with HHS.

Key Points Goals of therapy for hyperglycemic crisesimage

1. Restore hemodynamic stability, and replete whole-body electrolyte stores with fluid replacement.

2. Recover blood glucose control with insulin therapy.

3. Identify and start therapy for any precipitating illness.

4. Prevent hypophosphatemia and hypoglycemia.

5. Closely monitor for the complications that can occur during therapy.

Bibliography

1 Arora S., Henderson S.O., Long T., et al. Diagnostic accuracy of point-of-care testing for diabetic ketoacidosis at emergency-department triage: β-hydroxybutyrate versus the urine dipstick. Diabetes Care. 2011;34:852–854.

2 Canarie M.F., Bogue C.W., Banasiak K.J., et al. Decompensated hyperglycemic hyperosmolarity without significant ketoacidosis in the adolescent and young adult population. J Pediatr Endocrinol Metab. 2007;20:1115–1124.

3 Ennis E.D., Kreisberg R.A. Diabetic ketoacidosis and the hyperglycemic hyperosmolar syndrome. In: D LeRoith, SL Taylor, JM Olesfsky. Diabetes Mellitus: A Fundamental and Clinical Text. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2004:627–642.

4 Kitabchi A.E., Murphy M.B., Spencer J., et al. Is a priming dose of insulin necessary in a low-dose insulin protocol for the treatment of diabetic ketoacidosis? Diabetes Care. 2008;31:2081–2085.

5 Kitabchi A.E., Nyenwe A.E. Hyperglycemic crisis in diabetes mellitus: diabetic ketoacidosis and hyperglycemic hyperosmolar state. Endocrinol Metab Clin North Am. 2006;35:225–251.

6 Kitabchi A.E., Umpierrez G.E., Fisher J.N., et al. Thirty years of personal experience in hyperglycemic crisis: diabetic ketoacidosis and hyperglycemic hyperosmolar state. J Clin Endocrinol Metab. 2008;93:1541–1552.

7 Kitabchi A.E., Umpierrez G.E., Murphy M.B., et al. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2006;29:2739–2748.

8 Krane E.J., Rockoff M.A., Wallman J.K., et al. Subclinical brain swelling in children during treatment of diabetes ketoacidosis. N Engl J Med. 1985;312:1147–1151.

9 Morris L.R., Murphy M.B., Kitabchi A.E., et al. Bicarbonate therapy in severe diabetic ketoacidosis. Ann Intern Med. 1986;105:836–840.

10 Nugent B.W. Hyperosmolar hyperglycemic state. Emerg Med Clin North Am. 2005;23:629–648.

11 Orlowski J.P., Cramer C.L., Fiallos M.R. Diabetic ketoacidosis in the pediatric ICU. Pediatr Clin North Am. 2008;55:577–587.

12 Parker J.A., Conway D.L. Diabetic ketoacidosis in pregnancy. Obstet Gynecol Clin North Am. 2007;34:533–543.

13 Rosenbloom A.L. Hyperglycemic hyperosmolar state: an emerging pediatric problem. J Pediatr. 2010;156:180–184.

14 Savage M.W., Dhatariya K.K., Kilvert A., et al. Joint British Diabetes Societies guideline for the management of diabetic ketoacidosis. Diabet Med. 2011;28:508–511.

15 Umpierrez G. Narrative review: ketosis-prone type 2 diabetes mellitus. Ann Intern Med. 2006;144:350–357.

16 Usher-Smith J.A., Thompson M.J., Sharp S.J., et al. Factors associated with the presence of diabetic ketoacidosis at diagnosis of diabetes in children and young adults: a systematic review. BMJ. 2011;343:d4092.

17 Westphal S.A. The occurrence of diabetic ketoacidosis in non-insulin-dependent diabetes and newly diagnosed diabetic adults. Am J Med. 1996;101:19–24.

18 Wilson J.F. In the clinic. Diabetic ketoacidosis. Ann Intern Med. 2010;152:ITC1–ITC16.

19 Wolfsdorf J., Craig M.E., Daneman D., et al. Diabetic ketoacidosis in children and adolescents with diabetes. Pediatr Diabetes. 2009;10 Suppl 12:118–133.

20 Wyckoff J., Abrahamson M.J. Diabetic ketoacidosis and hyperosmolar hyperglycemic state. In: CR Kahn, GC Weir, GL King, et al. Joslin’s Diabetes Mellitus. 14th ed. Philadelphia: Lippincott Williams & Wilkins; 2005:887–899.

Related posts:

Intensive Care Unit Organization, Management, and Value Status Epilepticus Bronchoscopy Acute Bacterial Pneumonia Toxic Alcohol Poisoning Hemodynamic Monitoring